BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

BACKGROUND:Postoperative adjuvant chemotherapy is a common method for the treatment of gastric cancer,but the curative effect of chemotherapy in different patients varies considerably.A new pre-clinical treatment model is needed to guide personalized drug therapy for patients with gastric cancer.OBJECTIVE:To construct organoid model based on gastric cancer tissue and investigate its application in personalized drug screening.METHODS:The tissue samples of 20 patients with gastric cancer were collected,digested and decomposed,mixed with matrix glue,and cultured with organoid medium containing epidermal growth factor and fibroblast growth factor 10.Hematoxylin-eosin staining and immunohistochemical method were used to verify the homogeneity of pathological morphology and immune molecular markers of gastric cancer organoids and original tumor tissues.The feasibility of the established gastric cancer organoid model for drug screening was evaluated through drug sensitivity screening of six drugs including carboplatin,irinotecan,fluorouracil,oxaliplatin,paclitaxel,and epirubicin.RESULTS AND CONCLUSION:Fourteen organoids of gastric cancer cases were successfully cultured.There were individual differences in morphology and growth characteristics of organoids.All organoids could be stably passed through,froze and resuscitated.Gastric cancer organoids retained the same morphological features and immunomolecular expression as primary tumor tissues.Six organoids showed different drug sensitivities to six chemotherapy drugs,which initially confirmed the feasibility of gastric cancer organoids as a drug screening model in vitro.

Objective To investigate the epidemiology of chronic kidney disease (CKD) in patients with hypertension and diabetes mellitus in Kunming urban area.Methods A multistage cluster randomized sampling method was used to collect 400 randomly selected patients (community managed hypertension and diabetes mellitus) in community service centers in the 4 main urban districts of Kunming,Yunnan province.The subjects were screened for CKD by questionnaires,physical examinations,and microalbuminuria tests.Results A total of 343 people were surveyed.The prevalence of albuminuria,proteinuria by routine urinalysis,decreased glomerular filtration rate,and CKD prevalence were respectively 37.3％,12.2％,5.0％ and 39.1％.A total of 134 patients with CKD (134/343) were screened.Logistic regression analysis showed male (OR=2.312,95％CI 1.325-4.037,P=0.003),hyperuricemia (OR=1.751,95％ CI 1.109-2.765,P=0.016) and obesity (OR=2.150,95％ CI 1.115-4.146,P=0.022) were related to CKD.Conclusions The prevalences of CKD and albuminuria are 39.1％ and 37.3％ in patients with chronic diseases (hypertension and diabetes) in the main urban community of Kunming,Yunnan.Hyperuricemia,male and obesity are independent risk factors for CKD.

BACKGROUND: Evidence exists that inhibition of matrix metanoproteinase-2(MMP-2) secretion in the proliferating hernangioma tissue by transfection of adenovirus-active MMP-2(Ad-aMMP-2) cDNA would become an important means for treatment of proliferating hemangioma.OBJECTIVE: To investigate the influences of Ad-aMMP-2 cDNA transfection on human proliferating hemangioma growth in nude mice.DESIGN, TIME AND SETTING: A randomized, grouping, and controlled observation was performed in West China Hospital of Sichuan University between August 2003 and September 2004.MATERIALS: Eighteen BALB/c-nu/nu nude mice, weighing approximately 20 g, were included. Cavernous hemangioma specimen pathologically confirmed as proliferating hemangioma was resected from one 52-day-old female child patient.METHODS: The freshly reseoted human proliferating hemangioma specimen was sliced into small pieces with a size of 5 mm×4 mm×3 mm and subcutaneously implanted into the back of 18 nude mice within 1 hour to develop mouse models of hemangioma.Forty-five days after hemangioma implantation, 15 successful hemangioma nude mice were treated by intratumoral administration of adenovirus green fluorescent protein (Ad-GFP1 n = 51 Ad-GFP group), adenovirus-active MMP-2 (n = 5, Ad-aMMP-2 group), or the same amount of phosphate buffered saline (PBS1 n = 51 control group). Intratumoral administration was performed once every other day, for a total of 4 times.MAIN OUTCOME MEASURES: Observation of tumor volume and compadson of tumor necrosis area among 3 groups; detection of GFP expression in nude mouse; gross, hematoxylin-eosin staining, and transmission etectron microscope observation of tumor tissue morphology; determination of MMP-2 cDNA expression and microvascular density by immunohistochemistry; and detection of growth cycle and apoptosis of tumor cells by flow cytometry.RESULTS:①Ad-aMMP-2 could inhibit hemangioma growth in vivo, without marked adverse reactions. Tumor necrosis of different degrees was found in each group, and tumor necrosis area was significantly greater in the Ad-aMMP-2 group than in the control and Ad-GFP groups (P < 0.01). ②Histological sections displayed GFP gene expression in the Ad-GFP group. ③Gross observation results revealed relatively large tumor tissue in the control and Ad-GFP groups and relatively small tumor tissue in the Ad-aMMP-2 group. Hernatoxylin-eosin staining results showed that in the control and Ad-GFP groups, endothelial cells aggregated together in strip-shaped or lump-shaped appearance, and in the Ad-aMMP-2 group, there were many necrotic loci arranging in lamellar-shape appearance. Transmission electron microscope results revealed vascular endothelial cells with normal morphology in the control group and tumor cells with apparent nucleoli in the Ad-GFP group, while in the Ad-aMMP-2 group, some vascular endothelial cells exhibited chromatin pycnosis in the nucleus, forming apoptotic bodies.④ MMP-2 expression and microvascular density were significantly reduced in the Ad-aMMP-2 group than in the Ad-GFP and control groups (P < 0.05). ⑤The percentage of tumor cells in G0/G1 phase was significantly higher (P < 0.05), while the proliferating index was significantly decreased, in the Ad-aMMP-2 group than in the Ad-GFP and control groups. The Ad-aMMP-2 group exhibited higher apoptosis rate of tumor cells (P < 0.05), as well as more markedly increasing apoptosis index, than the control and Ad-GFP groups.CONCLUSION: It is feasible to block human proliferating hemangioma growth by transfeotion of Ad-aMMP-2 cDNA. The included mechanisms are to inhibit vascular endothelial cells to secrete MMP-21 thereby leading to local ischemia.